Coronary Heart Disease often leads to acute mycardial ischemia (Ml) and results in myocardial infarction. Published studies show that ischemia causes cell death, which plays a critical role in the development of cardiovascular disease. Results published show that nuclear factor kappa B (NF-kappaB) contributes to cell death after ischemia/reperfusion (I/R) and is cardioprotective after permanent coronary occlusion (PO) or late ischemic preconditioning (IPC). The primary objective is to distinguish and determine the mechanisms that underlie these differential effects of NF-kappaB after I/R vs. PO by studying infarct size and mode of cell death using assays to asess myocardial infarction and cell death (quantitative assays of apoptosis vs. necrosis). A secondary objective is to determine the sets of NF-kappaB regulated genes that underlie the differences in cardiac pathology vs. cardioprotection using various genetic (e.g. transgenic and knockout mice) and pharmacological approaches. The impact of the research is to identify novel therapeutic targets to enhance cardioprotection and to block cell death and/or inflammation resulting from ischemic injury. Identifying novel herapuetic targets for treatment of Ml is critical for reducing coronary heart disease.